Researchers have discovered a new autoimmune syndrome associated with COVID-19 that can cause life-threatening lung disease.
The syndrome – which scientists have dubbed “MDA5-autoimmunity and interstitial lung disease contemporary with the COVID-19 pandemic,” or MIP-C for short – is a rare and serious disease in which the immune system inadvertently attacks the body . In the worst cases, the lungs end up so scarred and stiff that the only way to save the patient is a full lung transplant.
However, only a portion of cases involve the lungs. “Two-thirds of our cases did not have lung disease,” said Dr. Dennis McGonagle, a rheumatologist at the University of Leeds in the United Kingdom, who was the first to reconstruct the characteristics of the new disease. “But we found that eight cases progressed rapidly and died despite all the high-tech therapies we were able to offer them.”
In total, McGonagle and colleagues have identified 60 cases of the syndrome so far. They published a study of the cases on May 8 in the journal eBioMedicine.
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The disease resembles the known disease MDA5 dermatomyositis, which almost entirely affects women of Asian descent, McGonagle told Live Science.
Patients there suffer from joint pain, muscle inflammation and skin rashes and, in two-thirds of cases, develop life-threatening lung scarring. MDA5 dermatomyositis occurs when the immune system attacks one of its own: a protein called MDA5 that normally helps detect RNA virus. These viruses include those that cause influenza, Ebola and COVID-19.
To better understand autoimmunity against MDA5, hospitals associated with the University of Leeds in Yorkshire have begun screening people with autoimmune symptoms. antibody against protein. In 2018, they found three patients who matched these criteria. They saw three more cases the following year and eight more in 2020 – but then, in 2021, there were suddenly 35.
The patients carried anti-MDA5 antibodies, but their disease was different from previously known dermatomyositis. Most cases did not involve the lungs; new patients were mostly white rather than Asian; and women affected were barely more numerous than men.
McGonagle contacted Dr Pradipta Ghosh at the University of California, San Diego to further his research. Ghosh used a computational framework to collect medical test data and find commonalities between conditions. His team has already published work on lung scarring in COVID-19as well as MISCELLANEOUS-Can inflammatory syndrome that occurs in some children after contracting COVID-19.
The team compared medical records of patients with this mysterious illness, patients with COVID-induced pneumonia, and patients with lung scarring unrelated to viruses. Patients with pneumonia and autoimmune disease both showed increased activity of the IFIH1 gene, which provides the template for MDA5.
Most patients with the mystery syndrome did not have a recently confirmed case of COVID-19 on their records, but it is likely that many were exposed to the coronavirus and had mild or asymptomatic illness, McGonagle said, being given the timing of their cases. More than half of patients have been confirmed vaccinated against COVID-19, although the specific vaccine each person received is unknown.
Related: Master regulator of inflammation discovered – and it’s in the brainstem
The new study suggests that exposure to coronavirus RNA, COVID-19 vaccines, or both can sometimes trigger the production of anti-MDA5 antibodies, McGonagle said.
Normally, MDA5 activates when it detects viral RNA in a cell and triggers the body to produce antibodies against the virus. But in people with PID-C, this immune response deteriorates. Either the body mistakes the MDA5 protein as foreign and attacks it, or the RNA triggers an immune response so strong that the body’s own proteins, including MDA5, become the target of an immune attack, McGonagle suggested.
The activation of IFIH1 was accompanied by an influx of an inflammatory protein called interleukin-15 (IL-15), the researchers found. IL-15 activates a class of immune cells that normally kill infected cells, but can sometimes lash out and attack the body’s own cells.
“Our work should encourage doctors to start thinking that if you find that there has been exposure to the virus or the vaccine or just contact with someone who has had COVID and they present with joint pain , rashes, body aches…let’s look at the lungs,” Ghosh told Live Science.
Researchers continue to collect data, but new cases of PID-C now appear to be slowing. In 2022, Yorkshire recorded 17 cases, around half the rate in 2021. Intense exposure to RNA during the widespread COVID waves of 2021 as well as mass vaccination may have driven this year’s peak – there, McGonagle theorized. The researchers said they had also received reports of possible MIP-C from other regions.
The study also discovered a particular genetic sequence within the IFIH1 gene that, in people with this sequence, appeared to prevent the uncontrolled IL-15 inflammatory response. The next step is to understand why others are vulnerable to it, Ghosh said.
This article is for informational purposes only and is not intended to offer medical advice.
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